J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.2.154 on 1 April 1967. Downloaded from J. Neurol. Neulrosurg. Psychiat., 1967, 30, 154 Insomnia after bilateral stereotactic thalamotomy in man

ALBINO BRICOLO From the Department of , City Hospital, Verona, Italy

We think it interesting to report a case of insomnia, CASE REPORT occurring in a Parkinsonian patient after bilateral stereotactic thalamotomy, as a clinical contribution This 58-year-old truck driver was in good health until to the physiopathology of variations of conscious- the onset of his present illness. He began to exhibit ness and regulation of the sleep-wakefulness symptoms of extrapyramidal Parkinsonism in 1958 rhythm. (rigidity, , and bradykinesia of the right hand). experimental findings in Within a year the same symptoms appeared in the right Neurophysiological lower limb also. At the same time he complained of animals suggest that in addition to the activating or hypersalivation and nondescript pain in the right shoulder. arousing mechanisms of the reticular formation, These symptoms became slowly but progressively worse deactivating or hypnogenic mechanisms, also local- until 1960, when the patient was forced to give up his job. Protected by copyright. ized in the brain-stem,' play a prominent part in the In the two years before admission to hospital the patient regulation of sleep-wakefulness alternation (Hess, developed a progressive nocturnal insomnia: soon after 1944; Moruzzi, 1963; Rossi, 1964 and 1965). This retiring he would experience vague pains and a pulling hypothesis rests on the observation that an enduring sensation in all extremities, with some indefinite visceral sleep-like state, as well as a long-lasting insomnia, disturbances that prevented sleep. Solitude, darkness, and may be produced by brain-stem lesions, the sign of silence seemed to aggravate the symptoms, so that the on the site of patient became increasingly anxious. His relatives con- the effect being dependent exclusively firmed that he was unable to sleep for several hours after the brain-stem damage (Batini, Magni, Palestini, going to bed, and that he got up very early in the morning Rossi, and Zanchetti, 1959a; Batini, Moruzzi, in a groggy and irritable mood. Unless he took daytime Palestini, Rossi, and Zanchetti, 1959b; Cordeau and naps, he would deteriorate over several days until a Mancia, 1959, Candia, Favale, Giussani, and Rossi, good night's sleep produced improvement. 1962a; Candia, Minobe, and Rossi, 1962b; Jouvet, On his first admission (8 January 1962) the patient 1962, 1965a, b and c; Minobe, Candia, and Rossi, appeared in good health; contributory physical findings 1962). were elicited only by neurological examination. He In man there is much clinical, E.E.G., and presented a marked right extrapyramidal syndrome with of a tremor, rigidity, and bradykinesia. He was entirely self-

to the existence http://jnnp.bmj.com/ anatomical evidence pointing sufficient. During the pre-operative period we observed passive mechanism for the reduction of conscious- the sleep pattern reported above. ness; conversely, evidence supporting the theory of Routine laboratory tests as well as and chest an active mechanism is scanty and not nearly so radiographs contributed nothing. On 16 January left convincing. In fact, in neurosurgical and neuro- chemothalamectomy was done under local anaesthesia by logical experience, reduction of consciousness and Cooper's method. The pneumoencephalogram showed a vigilance levels (drowsiness, obnubilation, hyper- fairly well-expanded , with enlarge- somnia, coma, and prolonged coma) as a conse- ment of the left ventricle. A lesion was made in the region is of the nucleus ventralis lateralis (V.L.) by inflating a quence of more or less localized brain lesions, on October 4, 2021 by guest. frequently observed, while it is rare to find the oppos- standard 7 mm. balloon (Fig. 1). With inflation, tremor more often, and rigidity of the contralateral extremities were com- ite condition of insomnia. The latter or, pletely relieved. The following day the procedure was inversion ofsleep rhythm, has been reported to follow completed by injection of alcohol. The post-operative diffuse rather than focal lesions (see the classical course was uneventful. At the time of discharge on 25 works of Von Economo, 1929 and 1930); these cases January the patient was well and his insomnia had are of little interest to those who wish to determine a disappeared. structural site for the neurophysiological mechan- The results of thalamectomy were consolidated in time; isms responsible for changes in the vigilance level. two months later he stated in a letter that he was 'com- 154 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.2.154 on 1 April 1967. Downloaded from Insomnia after bilateral stereotactic thalamotomy in man 155 *0- 19 -1s LEFT CHEMOTHALAMECTOMY RIGHT CRYOTHALAMOTOMY (jan. 16.1962) (Apr. 13.1964)

FIG. 1. Schematic representation ofportions of ventricular system, with landmarks of the anterior and posterior com- missure (AC and PC) and site ofthalamic surgical lesions. pletely well', able to use his right limbs normally, and unbearable agitation and remained lucid and not at all Protected by copyright. free of insomnia. After about a year he began to complain somnolent. The third night was again sleepless. At 9 p.m. of tremor, rigidity, and difficulty in moving the left surface electrodes were placed on his head and on the extremities, with occasional in the right limbs. periorbital region and a polygraphic recording was Slowly but progressively the Parkinsonian symptoms in started. Unfortunately after 20 minutes this had to be the left side increased, while the right side remained discontinued because the patient was rebellious and tore unimpaired. Sleep also remained normal. off the electrodes, and behaved aggressively toward the On his second admission (8 April 1964) his general physicians and nursing staff. Once he was again free to condition was good. Extrapyramidal Parkinsonian move he acted as on the previous night, complaining of syndrome was present with tremor, rigidity, and marked vague pains, anxiety, and shaking nervousness. The akinesia of the left-side limbs; episodic mild tremor of the E.E.G. tracings obtained in the first 20 minutes were right extremities was also observed. He was entirely self- diffusely desynchronized, with no reaction to opening and sufficient. No sleeping difficulty was noticed during closing of the eyes (Fig. 2). The next day he was extremely clinical observation. tense, panicky, and intolerant of even the slightest noise Laboratory tests still gave no information. On 13 April and visual stimuli; his general condition had deteriorated right cryothalamotomy was performed under local and he could maintain the standing position only if anaesthesia. The pneumoencephalogram showed no assisted. On the fourth night generous doses of barbitur- change since 1962. The area of the right V.L. was frozen ates and perphenazine were given. The patient relaxed (with the target more medial and more posterior than the but was still unable to fall asleep, though he was obviously http://jnnp.bmj.com/ contralateral lesion) and immediate resolution of left- exhausted. Only at about 10 a.m. the next morning did he side tremor and rigidity was thus produced (Fig. 1). fall into an apparently deep sleep of about three hours' After an uneventful first day, the patient could not go to duration,with short awakenings between. He awoke much sleep; he finally got out of bed and spent the rest of the relieved and remained relaxed enough to take several night fretting in an armchair. The next morning he looked naps during the day, whenever conditions permitted. At tired and presented a masked facies, though he was night, however, he was again fully awake and sleepless, lucid and well orientated; active motility remained good. and spent the whole fifth night without sleeping. This During the second post-operative day he was wide awake, insomnia, however, was offset by daytime drowsiness and and at night he was still fully alert, tense, and incapable of morning naps on the sixth day. Once more, the patient on October 4, 2021 by guest. going to sleep; he asked for sleeping pills. During the was sleepless on the sixth night, but this time he was able next several hours he was given 300 mg. of phenobarbital to fall asleep at approximately 1 a.m.; this was his first orally and 100 mg. of perphenazine intramuscularly; instance of spontaneous nocturnal sleep since the opera- nevertheless, he became increasingly anxious, restless, tion, and was followed by shorter naps at dawn. During and agitated. He spent the whole night awake, although the ensuing morning he was in a happier mood, with less the environment was made as comfortable and restful as daytime drowsiness. On the seventh day it was possible to possible. The following day (third post-operative day), he take an uninterrupted recording of the E.E.G., heart rate, was noticeably anxious and prostrated; he complained of and eyes movements during 14 consecutive hours, from J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.2.154 on 1 April 1967. Downloaded from

156 156 Albino Bricolo

1-4

2-6 EYES OPEN EYES CLOSED

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FIG. 2. E.E.G. recorded during the third sleepless nighit.

~~~~~~~~~~~~~~~~~~~~~~IfllIY U~~H http://jnnp.bmj.com/ TiME 60 120' 18 240' 300' 360 420'

VI I H VI dSI o 2 §'3 14 TIME 4800' 540' 600' 660' 720 780' 840' FIG. 3. Diagrammatic representation ofsleep through a polygraphic recording (E.E.G., E.K.G., and E.M.) from 10p.m. on October 4, 2021 by guest. of the seventh post-operative night to 12 noon the following day. According to the simplified scheme proposed by Pisano, Rosadini, Rossi, and Zattoni (1964, 1966) and by the French authors (Tissot, 1965, and others) sleep was subdivided into four phases having thefollo wing electrographic characters: phase 1, disappearance ofthe alpha rhythm in the E.E.G. and appearance of low-voltage, irregular, though chieflyfast activity with some 4-6/sec. waves but no significant eye move- ments; phase 2,spindles and some 3-6/sec. waves in the E.E.G. but no eye movements; phase 3, very slow (1-3/sec.) waves of high amplitude in the E.E.G. and no eye movements; phase 4, E.E.G. similar to that recorded in phase 1, though often with peculiar bursts of saw-toothed waves at 3-4/sec. in thefrontal leads; typical rapid movements of the eyes (Dement andKleitman, 1957; Jouvet, Michel, and Mounir, 1960; Jouvet, 1965a, b, andc). 'W' = awake. Recording time = 840 min; total wakefulness time = 570 min. (67-8 % ofrecording time); total sleep time = 270 min. (13.1 %). Total time for each phase: phase 1 = 96 min. (355 % ofsleep time); phase 2 = 8 min. (2-9 %); phase 3 = 166 min. (61-4%); phase 4 = 0. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.2.154 on 1 April 1967. Downloaded from

Insomnia after bilateral stereotactic thalamotomy in man 157 10 p.m. to 12 noon on the following day. As shown in rostral portion of the ventralis posterior medially Fig. 3, the sleep rhythm in this case was abnormal with reaching the centro-medianus and arriving at the regard to phase sequence as well as in each single phase: dorsal boundaries of the subthalamus. The second phases 1 and 3 were markedly prolonged, phase 2 was thalamic lesion delivered in the right side by a poorly represented, and phase 4 was missing altogether. In the following days the patient's sleep-wakefulness cryogenic system probably involved the ventralis rhythm gradually became more regular; however, he still lateralis (to a lesser extent), the ventralis intermedius, required a fairly long time to fall asleep. Unfortunately, the centro-medianus, the rostral portion of the we were unable to secure further E.E.G. recordings be- ventralis posterior, and the subthalamus, including cause of the patient's refusal. On discharge, 27 days after the dento-rubro-thalamic bundle and Forel's HI surgery, tremor and rigidity of the left extremities were field. completely relieved; there was a slight residual brady- With the limitation stated above, we believe that kinesia, but functional recuperation of the left upper limb this case of unusual insomnia corroborates the was satisfactory, and the state of anxiety had abated. hypothesis that the , especially the non- Follow-up examination on several occasions showed no of the recurrence of tremor and rigidity; conversely, a slowly specific nuclei thalamus, is instrumental in the progressing akinesia was noted. The patient reported implementation of sleep-inducing mechanisms that he was still having sleeping difficulties, approximately (Rossi, 1962). as before the first operation. He takes sedatives regularly. SUMMARY DISCUSSION An unusual case of total and irreducible insomnia in a Parkinsonian patient after bilateral stereotactic From our experience of over 1,000 stereotactic thalamotomy is reported. thalamotomies, 500 of which were bilateral, we find During 96 hours of total (night and day) insomnia that sleep disturbances are frequent in Parkinsonian the patient's behaviour differed from that of persons Protected by copyright. patients: many of them complain of nocturnal experimentally deprived of sleep by showing no reduction of sleep and induction insomnia or, less capacity for sleeping; he was fully alert and well commonly, of daytime drowsiness. Generally orientated. Subsequently the patient presented thalamotomy modifies such disturbances: in the inversion of the sleep-wakefulness rhythm, which acute post-operative phase there may be many progressively became more regular. A polygraphic changes of consciousness, levels ranging from a recording during the recovery stage showed ab- state of extremely prolonged vigilance to hyper- normal sleep: phases 1 and 3 were markedly pro- somnia and coma. Inversion of the sleep-wakeful- longed, phase 2 was poorly represented, and phase 4 ness rhythm is also frequent during this phase, with was missing altogether. The stereotactic lesions, a remarkable reduction in nocturnal sleep and bilaterally delivered to the thalamus, involved, prolonged daytime drowsiness. These disturbances besides the ventralis lateralis, the ventralis inter- usually abate rapidly and the patient returns to his medius, partially the ventralis posterior, and the normal level of consciousness with a regular sleep centro-medianus, other nuclei of the so-called non- rhythm. Similar modifications, perhaps slightly more specific projection system. accentuated, occur after bilateral thalamotomy. This case may indicate that the thalamus, especi- Our experience, therefore, indicates that the

ally the non-specific thalamus, is involved in the http://jnnp.bmj.com/ thalamus (thalamic nuclei or crossing fibres?) is determination of sleep induction. involved in the regulation of the sleep-wakefulness rhythm. REFERENCES The case reported here is remarkable inasmuch as Batini, C., Magni, F., Palestini, M., Rossi, G. F., and Zanchetti, A. it is the only one in our own experience entailing (1959a). Neural mechanisms underlying the enduring EEG and total and prolonged loss of sleeping capacity. behavioral activation in the midpontine pretrigeminal cat. Arch. ital. Biol., 97, 13-25. Identification of the anatomical structures respons- Moruzzi, G., Palestini, M., Rossi, G. F., and Zanchetti, A. ible for insomnia in this patient, and hence its (1959b). Effects of complete pontine transections on the sleep- on October 4, 2021 by guest. pathological interpretation, is difficult on account wakefulness rhythm: the midpontine pretrigeminal preparation. Ibid., 97, 1-12. of the well-known limitations inherent in human Candia, O., Favale, E., Giussani, A., and Rossi, G. F. (1962a). Blood stereotaxis, particularly as regards precise anatomical pressure during natural sleep and during sleep induced by electrical stimulation of the brain stem reticular formation. recognition of target structures due to individual Ibid., 100, 216-233. variability. Minobe, K., and Rossi, G. F. (1962b). Persistente insonnia da lesioni chirurgiche sperimentali del ponte. Boll. Soc. ital. Biol. The lesion delivered in the left side by Cooper's sper., 38, 1139-1141. chemothalamectomy in this case most probably Cordeau, J. P., and Mancia, M. (1959). Evidence for the existence of involved the medio-ventral portion of the ventralis an electroencephalographic synchronization mechanism originating in the lower brain stem. Electroenceph. clin. lateralis, most of the ventralis intermedius, and the Neurophysiol., 11, 551-564. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.30.2.154 on 1 April 1967. Downloaded from

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